Gallic acid intake induces alterations to systems metabolism in rats6

Gallic acid (GA) and its metabolites are polyphenolic compounds present in daily diets and herbal medicines. To understand the GA effects on the endogenous metabolism of mammals, we systematically analyzed the metabonomic responses of rat plasma, liver, urine, and feces to a single GA dosage of 120 and 600 mg/kg, which were below the no-obvious-adverse-effect-level of 1 g/kg for rats. Clinical chemistry and histopathological assessments were conducted to provide complementary information. Our results showed that GA intake induced significant metabonomic changes in multiple rat biological matrices. Such changes were more outstanding in liver than in the other matrices and clearly showed dose- and time-dependence. The results suggested GA-induced promotion of oxidative stress as the major effect. High-dose GA caused significant metabolic changes involving glycogenolysis, glycolysis, TCA cycle, and metabolism of amino acids, purines, and pyrimidines, together with gut microbiota functions. Low-dose GA only caused some urinary metabonomic changes and to a much less degree. The GA-induced liver metabonomic changes were not completely recoverable within a week, although such recovery completed in plasma, urine, and feces within 80 h. These findings provided new essential information on the effects of dietary polyphenols and demonstrated the great potential of this nutrimetabonomics approach.